Streamlining ICH Q6B Analytical Testing of Biotherapeutics

Abstract

ICH Q6B is a useful guide for determining appropriate analytical testing of a biotherapeutic. This document describes an approach to streamlining this testing by selecting a short list of the most powerful analytical methods early in development and the use of universal methods. Universal methods are designed to provide useful data for the majority of protein therapeutics. Some of these universal methods include size exclusion chromatography for the determination of aggregation and degradation products, ion exchange HPLC for the determination of charge variants and oligosaccharide profiling for glycosylated therapeutics. This allows for more testing earlier without spending time and money optimizing methods for a particular drug. The authors discuss how to determine what testing is required in early development, how to know when more testing is required and when more optimization of the universal methods is warranted. Data will be shown to demonstrate how the same assay can be used from initial lot-to-lot comparisons through assay validation and a full characterization of the therapeutic. For example, N-linked oligosaccharide profiling by HPLC is a relatively quick and simple means of evaluating the glycosylation of a biotherapeutic using chromatographic peak areas. Understanding the heterogeneity of the glycosylation early in product development from lot –tolot comparisons, along with bioassay, in vivo and pre-clinical testing, is an effective way of defining the window for the product’s critical quality attributes. Further along in development, the N-linked profiling assay can be used to quantitate the heterogeneity of the glycosylation and the oligosaccharide peaks can then be collected and identified by mass spectrometry, glycosidase sequencing and other methods.